International Journal of Research and Development in Pharmacy and Life Sciences

Available online at http//www.ijrdpl.com

June - July, 2015, Vol. 4, No.4, pp 1620-1624
ISSN (P): 2393-932X, ISSN (E): 2278-0238

Review Article

EPIDEMIOLOGIC EVIDENCE OF GASTRIC CANCER PROGNOSIS: ROLE OF DIETARY FACTORS

Soumee Ghosh#1, Sudakshina Ghosh#1, Srikanta Guria2, Subrata Chakraborty1 and Madhusudan Das*1
1. Department of Zoology, University of Calcutta, 35 Ballygunge, Circular Road, Kolkata 700 019, India.
2. Department of Zoology, Barasat Govt. College, Barasat, Kolkata 700124, India.
#
Equal contribution
*Corresponding Author: Email [email protected]
(Received: April 14, 2015; Accepted: May 04, 2015)

ABSTRACT
There are geographic and ethnic differences in the incidence of gastric cancer around the world as well as with its trends for each population over time.
The incidence patterns observed among immigrants change according to where they live. All of these factors indicate the close association of gastric cancer with
diet. This review presents epidemiological evidence on the association between dietary factors and gastric cancer. Infection with Helicobacter pylori is a strong risk
factor of gastric cancer however smoking, alcohol, diet, genetics and epigenetic factors may also play a role in the occurrence of this disease. The risk may be
increased with a high intake of various traditional salt-preserved foods and decreased with a high intake of fruit and vegetables. Among them, vitamin C is a
probable candidate supported by a relatively large group of epidemiological evidence. Consumption of green tea is possibly associated with a decreased risk of
gastric cancer. In contrast, processed meat and N-nitroso compounds may be positively associated with the risk of gastric cancer. In conclusion, dietary modification
by reducing salt and salted food intake, as well as by increasing intake of fruit and vitamin C, represents a practical strategy to prevent gastric cancer.
Keywords: Dietary habits, Gastric Cancer, Helicobacter pylori.

INTRODUCTION Dietary factors like pickled food, food rich in nitrite and high
Gastric cancer, a malignant tumour arises from the lining of salt concentration and smoked food are reported to increase
the stomach. It is considered as one of the most prevalent the risk. On the other hand it has been reported that black
cancers throughout the world, and ranks second in terms of tea reduces the risk of gastric cancer due to its antioxidant
cancer related deaths1. Worldwide it causes approximately properties5. In this review, we present epidemiological
700,000 deaths every year2. In most of the cases it is either evidence for the association between dietary factors and
asymptomatic or may cause only nonspecific symptoms in its gastric cancer, with particular reference to our recent work in
early stages. So, by the time symptoms occur, carcinogenesis our lab.
process often reaches an advanced stage and may also Dietary habit and gastric cancer in India
metastasize which is one of the main reasons for its relatively Gastric Cancer is considered as one of the most prevalent
poor prognosis. Infection with Helicobacter pylori is an cancer throughout the world, and ranks second in terms of
established cause; however smoking, alcohol, diet, genetics cancer related deaths (WHO). In India, the incidence of
and epigenetic factors may also play a role in the gastric cancer is overall less compared to the world.
occurrence of this disease3,4. Various worldwide However, in Kashmir valley, it is amongst the first five cancers
epidemiological studies have shown that there is a close with a male dominance (Male: Female - 3.17:1). Studies
correlation between diet and gastric cancer development. show that dietary factors are probably the main reason for

©SRDE Group, All Rights Reserved. Int. J. Res. Dev. Pharm. L. Sci. 1620
 Das M. et. al., June- July, 2015, 4(4), 1620-1624

its high incidence. Consumption of high salt content including respectively10.The high prevalence of gastric cancer in
salted tea and food along with Helicobacter pylori infection Mizoram has mainly been attributed to dietary and unknown
may be the possible reasons for the high incidence of gastric genetic interactions.
cancer in the Kashmiri population. Drinking of salted tea is a Dietary Risk Factors for Gastric Cancer
typical habit among this population. Green tea is boiled in Epidemiologic studies throughout the world have shown a
water for long along with a pinch of sodium bicarbonate. It is relationship between diet and gastric cancer risk. The diets
then subjected to brewing until a reddish brown coloured that are most commonly linked to high gastric cancer risk are
extract is obtained. This salted alkaline solution is stored for those that are rich in salted, pickled, smoked or poorly
a long period and used over for many days. Later it is preserved foods, those with high meat content and those with
mixed with water, salt and milk and taken in hot condition. low fruit and vegetable content3. A link between high salt
Consumption of even more than 10 cups of this tea a day is consumption and increased gastric cancer risk has been
a common phenomenon. In a study on Kashmiri population, reported in numerous studies3. Dietary salt intake varies
Qurieshi et al showed that more than 2/3rd of the gastric widely among humans, and in some populations with a high
cancer patients consumed more than 4 cups of salted tea per incidence of gastric cancer, median dietary salt intakes of 46
day6. A study from North India carried out on Kashmiri g per day have been reported11.In Colombia, the
population between 2009 and 2011 recorded 776 gastric consumption of high levels of salt (as measured by high
cancer patients (590 males and 186 females) having a urinary sodiumto- creatinine ratios) was associated with an
median age of 55 and 60 years for males and females increased risk for precancerous gastric lesions (chronic
respectively. The age-adjusted rate (AAR) of gastric cancer atrophic gastritis, intestinal metaplasia and dysplasia)
among urban areas of India is (3.0–13.2) compared to the compared with what is observed in persons who consume
worldwide AAR (4.1–95.5).Worldwide, there has been a lower levels of salt12. Additionally, a prospective study of a
decline in the incidence of gastric cancer in the developed Japanese population, conducted over a 14 y period,
countries and this has been attributed to improved food reported that H. pylori-infected subjects consuming a high-
hygiene, sanitation, and food preservation techniques. But, salt diet had an increased risk of gastric cancer when
this declining trend has not been seen in certain parts of compared with H. pylori-infected subjects who consumed
India7.The regional variation in incidence of gastric cancer lower levels of salt13.Vitamin C has also been studied as a
can be ascertained by the fact that gastric cancer in South potential protective factor against the development of
Indian males has been reported to be more common than gastric cancer, likely through its antioxidant effects. Higher
their North Indian counterparts 8. Differences in dietary plasma levels of vitamin C have been associated with a
pattern along with use of alcohol and tobacco are lower risk for gastric cancer, irrespective of anatomic
considered to be potential risk factors. In a case–control site14.Epidemiological evidence supports the premise that
study from Trivandrum, excess consumption of rice and chili, both H. pylori and obesity are independent risk factors for
together with the consumption of high-temperature food gastric cancer15.Obesity induced inflammation underlies
were found to be independent risk factors for gastric cancer increasingly common diseases, such as type II diabetes and
in multivariate analysis9. The incidence of gastric cancer in atherosclerosis16. Importantly, several studies employing
Mizoram has been reported to be the highest in India. The mouse models and focusing on the direct effect of adipose-
AAR in males and females are reported at 50.6 and 23.3, derived factors on established tumors, have shown that
respectively [Indian Council of Medical Research (ICMR), First obesity promotes cancers (e.g. colorectal and pancreatic
Report of the Population Based Cancer Registries Under cancer) and implicate systemic inflammation as an important
North Eastern Regional Cancer Registry 2003-2004].In component of the tumorigenic process 17. Studies have
Mizoram, gastric cancer accounts for 30% of all cancer cases supported the protective role of dietary folic acid against
with a male-to-female ratio being 2.3:1; the median age for specified cancers18. A recent study also found that high
males and females was 58 years and 57 years dietary folate increased survival rates in gastric cancer

©SRDE Group, All Rights Reserved. Int. J. Res. Dev. Pharm. L. Sci. 1621
 Das M. et. al., June- July, 2015, 4(4), 1620-1624

patients compared with low folic acid intake in advanced Diet and Helicobacter pylori-induced gastric cancer
gastric cancer19. Green tea contains polyphenols, more CagA affects multiple signaling pathways within gastric
commonly known as catechins. Antioxidant activities and the epithelial cells23. CagA is translocated into host epithelial
ability to inhibit the nitrosation of polyphenols have been cells by the cag type IV secretion system and activates β-
isolated from green tea in both in vitro and in vivo studies20. catenin, leading to transcriptional up regulation of genes
In addition, recent research has proposed many other implicated in cancer. The CagA protein of certain H. pylori
possible mechanisms for the cancer inhibitory effects of strains also can induce NFκB activation. Thus, the entry of
green tea, including modulation of signal transduction CagA into host cells activates multiple signaling pathways
pathways, leading to the inhibition of cell proliferation and that may increase the risk for malignant transformation (Fig
transformation, induction of apoptosis and cell cycle arrest, 2)23.
and inhibition of tumor invasion and angiogenesis 21. Fruit and Iron Deficiency and Gastric Cancer Risk
vegetables are rich sources of vitamin C. Vitamin C acts as Iron deficiency is associated with an increased risk for gastric
an antioxidant and can quench reactive oxygen species cancer, as well as neoplasms that arise elsewhere in the
produced in the gastric environment. It is also known to inhibit gastrointestinal tract24. There are multiple mechanisms
production of carcinogenic N-nitroso compound in the through which iron deficiency may arise, including blood loss
stomach (Fig 1)22 . and dietary deficiency of iron. Among the many possible

Figure 1: inhibition of production of carcinogenic N-nitroso compound in the stomach

Figure 2: Helicobacter pylori-induced gastric cancer pathway

©SRDE Group, All Rights Reserved. Int. J. Res. Dev. Pharm. L. Sci. 1622
 Das M. et. al., June- July, 2015, 4(4), 1620-1624

causes of blood loss, colonization by certain H. pylori strains some of our patients. Gastric cancer is a multifactorial
has been associated with hemorrhagic gastritis and a disease where various genetic, epigenetic and environmental
resulting loss of iron25.A recent study analysed the effect of factors may interact in the prognosis of the carcinogenic
dietary iron depletion on the development of H. pylori- progression. In our recently published review, we have tried
induced cancer in gerbils infected with a cagA+ H. pylori to assess whether excessive consumption of alcohol
strain26 .H. pylori infection induced more severe gastritis in contributes to the risk of cancer burden4. Thus our study also
iron-depleted gerbils than in iron-replete gerbils. Gastritis corroborates with the previously reported findings that
also developed earlier in H. pylori-infected iron depleted suggest certain dietary factors aggravate the progression of
gerbils compared with infected iron-replete gerbils26. gastric cancer.
CONCLUSION REFERENCES
Direct effects of several dietary constituents on the gastric 1. Hamilton JP, Meltzer SJ. (2006) Clin Gastroenterol
epithelium might either raise or lower the threshold for Hepatol. 4:416-425.
2. Parkin DM, Bray F, Ferlay J, Pisani P.(2005) CA Cancer
malignant transformation. Also dietary components might J Clin. 55: 74–108.
damage the gastric mucosa, allowing increased entry of 3. Tsugane S , Sasazuki S.(2007) Gastric Cancer. 10:75-
potent carcinogens inside the gastric tissue. Some dietary 83.
4. Ghosh S, Guria S, Das M. (2015) Proc Zool Soc. DOI
components are known to interact with immune receptors in
10.1007/s12595-014-0134-3
the intestine thereby regulating intestinal immunity. Dietary 5. Weisburger JH, Chung FL.(2002) Food Chem Toxicol
composition might influence the composition of the gastric .40:1145-1154.
6. Qurieshi MA, Masoodi MA, Kadla SA, Ahmad SZ,
micro biota, or favour the proliferation of Helicobacter
Gangadharan P.(2011) Asian Pac J Cancer Prev.
pylori variants. The composition of the diet may also 12(1): 303-307.
influence epigenetic alterations, as shown in a recent study 7. Pavithran K, Doval DC, Pandey KK.(2002) Gastric
which reported that dietary folic acid supplementation Cancer.5(4):240-243.
8. Malhotra SL. (1967) Gut. 8(4): 361-372.
protected against loss of global DNA methylation and 9. Mathew A, Gangadharan P, Varghese C, Nair
markedly reduced the development of gastric inflammation. MK.(2000) Eur J Cancer Prev. 9(2):989-997.
Dietary modification to reduce salt and salted food intake 10. Phukan RK, Narain K, Zomawia E, Hazarika NC,
Mahanta J. (2006) J Gastroenterol.41(5): 418-424.
and to increase intake of fruit, particularly vitamin C as well
11. Oiso T. (1975) Cancer Res.35: 3254-3258.
as quitting smoking represents an effective, practical, low- 12. Chen VW, Abu-Elyazeed RR, Zavala DE, Ktsanes VK,
cost means of preventing gastric cancer. In our laboratory, Haenszel W, Cuello C, Montes G, Correa P. (1990)
Nutr Cancer.13: 59-65.
we are screening gastric cancer patients for ADH1B, ALDH2,
13. Shikata K, Kiyohara Y, Kubo M, Yonemoto K, Ninomiya
CYP2E1, GSTM1, GSTT1, GSTP1, XRCC1 and TP53 genes T, Shirota T, Tanizaki Y, Doi Y, Tanaka K, Oishi
polymorphisms where dietary habits of patients are also Y.(2006) Int J Cancer.119: 196-201.
14. You WC, Zhang L, Gail MH, Chang YS, Liu WD, Ma JL,
taken into account. This is done to find whether specific food
Li JY, Jin ML, Hu YR, Yang CS.(2000) J Natl Cancer
habits actually modulate the risk of gastric cancer by Inst.92: 1607-1612.
interacting with the polymorphisms of study genes. In our 15. Ahmed N, Sechi LA. (2005) Ann Clin Microbiol
study population, we have observed a tendency of excessive Antimicrob. 4(1): doi:10.1186/1476-0711-4-1.
16. Kanneganti TD, Dixit VD.(2012) Nat Immunol.13: 707–
intake of certain food types like animal fat, high salt, pickle 712.
and salted tea among the patient group. Chili pepper intake 17. Moon HS, Liu X, Nagel JM, Chamberland JP,
may also be a risk factor for gastric cancer 27. Capsaicin, the Diakopoulos KN, Brinkoetter MT, Hatziapostolou M, Wu
Y, Robson SC, Iliopoulos D, Mantzoros CS. (2013) Gut.
active part of the chili can participate in the carcinogenic
62: 561–570.
process. It may act as an irritant to the mucosal layer of the 18. Kim YI. (2004) Cancer Epidemiol Biomarkers Prev. 13:
stomach. However, its erosive role in gastric mucosa remains 511–519.
19. Shitara K, Muro K, Ito S, Sawaki A, Tajika M, Kawai H,
controversial28. Although not statistically significant, yet we
Yokota T, Takahari D, Shibata T, Ura T, Ito H, Hosono S,
observed the tradition of excessive intake of chili among Kawase T, Watanabe M, Tajima K, Yatabe Y, Tanaka
©SRDE Group, All Rights Reserved. Int. J. Res. Dev. Pharm. L. Sci. 1623
 Das M. et. al., June- July, 2015, 4(4), 1620-1624

H, Matsuo K. (2010) Cancer Epidemiol Biomarkers Prev.

19: 1311–1319.
20. Wang ZY, Cheng SJ, Zhou ZC, Athar M, Khan WA,
Bickers DR. (1989) Mutat Res.,223: 273–285.
21. Yang CS, Maliakal P, Meng X.(2002) Annu Rev
Pharmacol Toxicol.42: 25–54.
22. Drake IM, Davies MJ, Mapstone NP, Dixon MF, Schorah
CJ, White KL, et al. (1996) Carcinogenesis. 17: 559–
562.
23. Cover TL, Peek RM Jr. (2013) Gut Microbes. 4(6):
482–493.
24. Nomura A, Chyou PH, Stemmermann GN. (1992)
Cancer Epidemiol Biomarkers Prev.1: 547-550.
25. Yip R, Limburg PJ, Ahlquist DA, Carpenter HA, O’Neill
A, Kruse D, Stitham S, Gold BD, Gunter EW, Looker
AC.(1997) JAMA. 277: 1135-1139.
26. Noto JM, Gaddy JA, Lee JY, Piazuelo MB, Friedman
DB, Colvin DC, Romero-Gallo J, Suarez G, Loh J,
Slaughter JC.(2013) J Clin Invest.123:479-492.
27. López-Carrillo L, Hernández Avila M, Dubrow R. (1994)
Am J Epidemiol.139(3): 263-271.
28. Bode AM, Dong Z.(2011) Cancer Res. 71(8): 2809-
2814.

©SRDE Group, All Rights Reserved. Int. J. Res. Dev. Pharm. L. Sci. 1624